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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS 

PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: William Cutchin, 703-305-7990

INSTRUCTIONS: Please utilize this outline in preparing the pesticide petition. In cases 

where the outline element does not apply, please insert “NA-Remove” and maintain 

the outline. Please do not change the margins, font, or format in your pesticide 

petition. Simply replace the instructions that appear in green, i.e., “[insert company 

name],” with the information specific to your action.

TEMPLATE:

Clariant Corporation

IN-10661

EPA has received a pesticide petition, IN-10661, from Exponent (1150 

Connecticut Ave., NW Suite 1100, Washington, DC 20036) on behalf of Clariant

Corporation (4000 Monroe Road, Charlotte, NC 28205) requesting, pursuant to section 

408(d) of the Federal Food, Drug, and Cosmetic Act(FFDCA), 21 U.S.C. 346a(d), to amend 

40 CFR part 180 to establish an exemption from the requirement of a tolerance for C.I. 

Pigment Yellow 1 (CAS RN 2512-29-0); butanamide, 2- (4-methyl-2-nitrophenyl) azo -3-

oxo-N-phenyl-, for use as a pesticide inert seed treatment ingredient not to exceed 10% 

wt/wt, under 40 CFR §180.920 pursuant to Section 408(d)(l) of the Federal Food, Drug, 
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and Cosmetic Act (FFDCA). EPA has approved C.I. Pigment Yellow 1 as an inert ingredient 

for non-food use pesticide formulations.

EPA has determined that the petition contains data or information regarding the 

elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated 

the sufficiency of the submitted data at this time or whether the data supports granting 

of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. Not applicable/Not required for the establishment of a

tolerance exemption for inert ingredients.

2. Analytical method. Not applicable/Not required for the establishment of a

tolerance exemption for inert ingredients.

3. Magnitude of residues. Not applicable/Not required for the establishment of a

tolerance exemption for inert ingredients.

B. Toxicological Profile

1. Acute toxicity. The Clariant Monoazo Chemical Safety Report (2012) report

submitted under the auspices of the EU Reach regulatory initiative reported the 

following acute toxicity data for C.I. Pigment Yellow 1: OECD 401 (rat acute oral) LD50 > 

10,000 mg/kg/day (EPA Toxicity Category IV, practically non-toxic); OECD 402 (rat acute 

dermal) LD50 > 2,000 mg/kg (EPA Toxicity Category III); OECD 404 (rabbit dermal 

irritation) non-irritating; OECD 405(rabbit acute eye irritation) non-irritating; OECD 429 

(mouse local lymph node assay) non-sensitizing.

2. Genotoxicty. C.I. Pigment Yellow 1 did not display mutagenic activity in the

following assays: AMES bacterial (OECD 471) assay with and without metabolic
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activation; Chinese hamster lung fibroblast cell micronucleus test (OECD 487, version 3)

with and without metabolic activation and negative and the mammalian cell gene

mutation assay (OECD 476) with and without metabolic activation.

3. Reproductive and developmental toxicity. C.I. Pigment Yellow 1 was 

administered to Wistar rats (11/sex/dose) by gavage in a Combined Repeated Dose 

Toxicity Study with a Reproduction/Developmental Toxicity Screening (OECD 422) at 

dose levels of 0 (vehicle control), 100, 300 and 1000 mg/kg bw/day (actual amount 

ingested). Based on these, the NOAEL (No Observed Adverse Effect Level) for general 

toxicity in males and females and for reproduction/developmental toxicity was 

considered to be 1000 mg/kg bw/day, the highest dose level used.

All animals survived the scheduled study period. Clinical effects included yellow

stained feces in all treated animals. No effects were seen in locomotor activity or in the 

functional observational battery. Body weight gain of male animals in the 300 and 1000 

mg/kg bw/day dose groups were dose-dependently and significantly reduced in the premating period. No differences in body weight gain were noted at any dose level during 

the remaining study period. Body weights of males in all dose groups were similar to the 

respective control values during the entire study period. Because reduction in body 

weight gain at the high- and mid-dose levels was reversible and did not cause significant 

changes in body weights, this effect was considered not to be adverse. Body weights 

and body weight gain of females were not affected by the treatment at any dose level. 

Food consumption was not affected by the treatment at any dose level. No test 

substance-related effects on hematology, clinical biochemistry, urinalysis, organ weights 

or histopathology were noted at any dose level.

Mating performance, fertility, corpora lutea count, duration of gestation, 

implantation rate and post-implantation loss, litter size or postnatal loss were not 

affected by the treatment with the test item. At the dose level of 1000 mg/kg bw/day, 

reduction in mean count of progressive sperms and increase in mean count of not 

motile sperms were noted. At the dose level of 300 mg/kg bw/day, increase in mean 

count of not motile sperms was noted. A significant dose dependent trend could not be 

established. In the absence of any findings during necropsy or histopathological 

examination of male reproductive organs as well as absence of any effects on 

reproduction, the differences in sperm motility were considered not to be adverse. 
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Sperm morphology and sperm count were not affected by the treatment at any dose 

level. No test item related findings were noted in pups during first litter check and 

during lactation at any dose level. No test substance-related findings were reported in 

sex ratio or pup weight and no findings were noted upon gross pathology.

4. Subchronic toxicity. The general systemic toxicity NOAEL from the 28-Day 

OECD 422 Combined Repeated Dose Toxicity Study with a Reproduction/Developmental

Toxicity Screening Test in rats was 1000 mg/kg body weight/day.

5. Chronic toxicity. No chronic toxicity data for C.I. Pigment Yellow 1 are 

available. Based on the Federal Register Notice (August 9, 2006, Volume 71, Number 

153, pages 45415-45424), the Agency stated that the preferred test for repeat-dose 

toxicity is the ''Combined Repeated Dose Toxicity Study with the 

Reproduction/Developmental Toxicity Screening Test (OECD Test Guideline 422)."

Therefore, an OECD 422 study has been submitted and the results are summarized 

under the Reproductive and Developmental Toxicity, Section 3, of this document.

6. Animal metabolism. There are no publically available mammalian metabolism 

data reported for C.I. Pigment Yellow 1, but it is unlikely that metabolism would result in

the production of toxic or carcinogenic metabolites (Levine, 1991). In the 2012 monoazo 

pigment REACh CSR Clariant proposed the following rationale to address the potential 

animal metabolism in humans. The rationale was published was based on toxicokinetic 

data for a structurally related monoazo pigment, C.I. Pigment Yellow 74; butanamide, 2-

[(2-methoxy-4-nitrophenyl)azo]-N-(2-methoxyphenyl)-3-oxo-, (CAS RN 6358-31-2).

"Toxicokinetic behaviour (absorption -distribution - metabolism -excretion) of 

the Monoazo Yellow Pigments has been investigated for Pigment Yellow 74 after 

single oral application, but no investigations have been performed with the other 

members of this category. The findings for Pigment Yellow 74 as well as the 

observations made in several toxicity studies together with the physico-chemical 

properties of the pigments of this category will be addressed in the following 

section and the impact of these findings on the toxicokinetic behavior of the 

Monoazo Yellow Pigments will be discussed.
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Toxicokinetics of Pigment Yellow 74 has been investigated in male Fischer 344 

rats which received 12.6 mg/kg Pigment Yellow 74 by gavage. Urine, feces, 

stomach contents, intestinal contents and various tissues have been collected 1, 

4, 24 and 48 hours after dosing. One and 4 hours after dosing most of the 

administered material was present in the gut contents and none was in the 

feces. 24 and 48 after dosing, most part of the administered substance was in 

the feces (about 86% after 48 hours). Detectable amounts (>3%) were only in 

those tissues directly in contact with the compound. No test compound was

found in samples of plasma, whole blood, liver, kidney, or lungs, even after 

administration of doses ten times larger. These data indicate that Pigment 

Yellow 74 is not bioavailable after oral application.

The findings from several toxicity studies with Monoazo Yellow Pigment 74 and 

the absence of any toxic effect in these studies also indicate that the members of 

this category are not bioavailable by either the oral or dermal routes of 

exposure.

The conclusion that the members of this category are not bioavailable after oral 

or dermal application is supported by the data on the physicochemical

properties: Monoazo Yellow Pigments are nearly insoluble in water (1.9 to 19.3 

ug/L) and only marginally soluble in octanol (0.12 to 14.9 mg/L). Due to this low 

solubility the members of this category are (nearly) not existent in a dissolved 

form on the skin or mucous membranes after dermal, oral or inhalative 

exposure, i.e. they could not be absorbed through the skin or mucous 

membrane..."

Additionally, the weight of the evidence of the experimental toxicology 

mutagenicity studies indicate that C.I. Pigment Yellow 1 is not mutagenic and likely not 

metabolized to any great extent. These data infer that the azo-group is stable and not 

cleaved and ; oxidation of the aromatic amine is not oxidized to generate carcinogenic 

metabolites
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7. Metabolite toxicology. Not required.

8. Endocrine disruption. C.I. Pigment Yellow 1 does not belong to a class of

chemicals known or suspected of having adverse effects on the estrogen receptor or

endocrine system.

C. Aggregate Exposure

1. Dietary exposure. While no specific crop residue information is available for

C.I. Pigment Yellow 1, on the basis of the proposed tolerance exemption and the 

physical chemical and environmental properties analysis, environmental persistence 

with resultant crop residues are not likely from the use of C.I. Pigment Yellow 1 as 

pesticide inert ingredients in seed treatment formulations under 40 CFR §180.920 at 

concentrations not to exceed 10%. The seed treatment formulations containing C.I. 

Pigment Yellow 1 will be applied directly to the seeds and if released into the 

environment, experimental Koc data (log Koc = 5.1) indicate that the pigment will bind 

tightly to soil and sediment and not be soluble in water. Under these conditions, it is 

unlikely that the pigment will be taken up by the germinated seedlings and translocated 

within the plant vascular system to result in crop residues and dietary exposures.

The conservative I-DEEM screening level model analysis for food + drinking water 

indicates that the exposure to C.I. Pigment Yellow 1 would be 0.4% of the chronic 

population adjusted dose (cPAD) for the U.S. general population while the highest 

exposure would be to children 1-2 yrs old at 1.4 % cPAD.

i. Food. The chronic dietary exposures estimated using I-DEEM are well below 

100% of the cPAD, and are therefore below EPA's established level of concern for all U.S. 

subpopulations.

ii. Drinking water. Drinking water is included in the I-DEEM exposure assessment 

and based on anticipated concentrations expected to be negligible.
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2. Non-dietary exposure. None

D. Cumulative Effects

EPA has not determined that C.I. Pigment Yellow 1 has a common mechanism of 

toxicity with other substances.

E. Safety Determination

1. U.S. population. Based on the conservative exposure estimates, there is a

reasonable certainty that no harm will result to the U.S. population from the aggregate

exposure to C.I. Pigment Yellow 1 used at 10% concentration in seed treatment

formulations with chronic dietary exposure estimated to be 0.4% cPAD for the general 

U.S. population.

2. Infants and children. The FFDCA Section 408 requires an additional tenfold

margin of safety for the protection of infants and children in case of threshold effects to

account for prenatal and postnatal toxicity, and an inadequate toxicity database. Where

an adequate and reliable database is available and there is a lack of evidence for 

increased susceptibility, the FQPA safety factor may be reduced or removed.

Based on available information discussed herein, Clariant, Inc. requests 

reduction of the FQPA safety factor to IX and that the additional tenfold safety factor for 

the protection of infants and children be removed. As described above the default 10X 

FQPA safety factor may be reduced to IX, and the cRfD is therefore equivalent to the 

cPAD.

• The availability of a scientifically sound and robust mammalian toxicology

database that includes acute, subchronic, and genotoxicity data. These test data

did not result in adverse developmental, reproductive or neurological endpoints 

or genotoxic effects.
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• Soil application and physicochemical/environmental properties indicate that 

crop residues and resultant dietary exposures are unlikely when C.I. Pigment 

Yellow 1 is used in seed treatment formulations at concentrations not to exceed 

10% wt./wt.

• I-DEEM modeling supports that the estimated dietary exposures to C.I. 

Pigment Yellow 1 (used at 10% concentration in seed treatments) for children 1-

2 years of age, the potentially most exposed population, is 1.4 % and thus well 

below 100% of the cPAD.

• C.I. Pigment Yellow 1 does not belong to a class of chemicals that is known or 

suspected to affect the estrogen receptor or having any adverse effects on the 

endocrine system.]

F. International Tolerances

There are no known international tolerances for C.I. Pigment Yellow 1.